Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

Brain Structural Correlates of Obstacle Negotiation in Mild Cognitive Impairment: Results from the Gait and Brain Study.

INTRODUCTION: Mild cognitive impairment (MCI) affects obstacle negotiation capabilities, potentially increasing the risk of falls in older adults. However, it is unclear whether smaller brain volumes typically observed in older individuals with MCI are related to the observed hazardous obstacle negotiation in this population. METHODS: A total of 93 participants (71.9 ± 5.36 years of age; MCI = 53/control = 40) from the Gait and Brain Study were analyzed. Gray matter (GM) volumes from the frontal, temporal, and parietal lobes were entered in the analysis. Gait performance was recorded using a 6-m electronic walkway during two cognitive load conditions while approaching and stepping over an obstacle: (1) single-task and (2) while counting backwards by 1s from 100 (dual-task). Anticipatory adjustments in gait performance to cross an "ad hoc" obstacle were electronically measured during pre-crossing phases: early (3 steps before the late phase) and late (3 steps before obstacle). Association between the percentage of change in average gait speed and step length from early to late (i.e., anticipatory adjustments) and GM volumes was investigated using multivariate models adjusted for potential confounders. RESULTS: Anticipatory adjustments in gait speed (Wilks' lambda: 0.35; Eta2: 0.64; p = 0.01) and step length (Wilks' lambda: 0.33; Eta2: 0.66; p = 0.01) during dual-task conditions were globally associated with GM volumes in MCI. Individuals with MCI with smaller GM volumes in the left inferior frontal gyrus, left hippocampus, right hippocampus, and right entorhinal cortex made significantly fewer anticipatory gait adjustments prior to crossing the obstacle. CONCLUSION: Frontotemporal atrophy may affect obstacle negotiation capabilities potentially increasing the risk of falls in MCI.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Effects of multicomponent and dual-task exercise on falls in nursing homes: The AgeingOn Dual-Task study.

OBJECTIVE: To compare the effects of a multicomponent exercise program and a dual-task exercise program on the number of falls (fall rate) and number of fallers (fall incidence) and on parameters associated with fall risk in older adults living in long-term nursing homes (LTNH). STUDY DESIGN: This is a secondary analysis of a single-blind randomized controlled trial involving 85 older adults in nine LTNHs (Gipuzkoa, Spain). Participants allocated to the multicomponent group underwent a twice-a-week 3-month individualized and progressive resistance and balance program. The dual-task group performed simultaneous cognitive training with the same multicomponent exercises. MAIN OUTCOMES: Fall rate and incidence were analyzed using Poisson regression (adjusting for cognitive function and previous fall rate) and Kaplan-Meier analysis, respectively. Handgrip asymmetry, single- and dual-task TUG velocity and cost were assessed using two-way ANOVA for repeated measures and paired Student's t-tests. RESULTS: The dual-task group showed a 3.8 times greater risk of falling than the multicomponent group during the intervention, and a 2.59 times greater risk during the 12-month follow-up. There were no between-group differences in fall incidence. There were between-group differences in handgrip strength asymmetry in favor of the multicomponent group. While only the multicomponent group improved on the TUG test, the dual-task group improved on dual-task cost. CONCLUSIONS: Compared with the dual-task program, the multicomponent exercise program showed more benefits in reducing falls and in parameters associated with fall risk in LTNH residents. Future studies are warranted to confirm our results and continue to explore physical and cognitive interventions to prevent falls in LTNHs. Australian New Zealand Clinical Trials Registry ACTRN12618000536268.

Associations of Multidomain Interventions With Improvements in Cognition in Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

Importance: Older adults with mild cognitive impairment (MCI) have the highest risk of progressing to dementia. Evidence suggests that nonpharmacological, single-domain interventions can prevent or delay progressive declines, but it is unclear whether greater cognitive benefits arise from multidomain interventions. Objective: To determine whether multidomain interventions, composed of 2 or more interventions, are associated with greater improvements in cognition among older adults with MCI than a single intervention on its own. Data Sources: MEDLINE, Embase, PsycInfo, AgeLine, CINAHL, and Cochrane Central Register of Controlled Trials were systematically searched from database inception to December 20, 2021. Study Selection: Included studies contained (1) an MCI diagnosis; (2) nonpharmacological, multidomain interventions that were compared with a single active control; (3) older adults aged 65 years and older; and (4) randomized clinical trials. Data Extraction and Synthesis: Data were screened and extracted by 3 independent reviewers. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, random-effects meta-analyses were used to calculate effect sizes from the standardized mean difference (SMD) and 95% CIs. Main Outcomes and Measures: Postintervention cognitive test scores in 7 cognitive domains were compared between single-domain and multidomain groups. Exposure to the intervention was analyzed. Results: A total of 28 studies published between 2011 and 2021, including 2711 older adults with MCI, reported greater effect sizes in the multidomain group for global cognition (SMD, 0.41; 95% CI, 0.23-0.59; P < .001), executive function (SMD, 0.20; 95% CI, 0.04-0.36; P = .01), memory (SMD, 0.29; 95% CI, 0.14-0.45; P < .001), and verbal fluency (SMD, 0.30; 95% CI, 0.12-0.49; P = .001). The Mini-Mental State Examination (SMD, 0.40; 95% CI, 0.17-0.64; P < .001), category verbal fluency test (SMD, 0.34; 95% CI, 0.13-0.56; P = .002), Trail Making Test-B (SMD, 0.46; 95% CI, 0.13-0.80; P = .007), and Wechsler Memory Scale-Logical Memory I (SMD, 0.47; 95% CI, 0.15-0.80; P < .001) and II (SMD, 0.26; 95% CI, 0.07-0.45; P < .001) favored the multidomain group. Exposure to the intervention varied between studies: the mean (SD) duration was 71.3 (36.0) minutes for 19.8 (14.6) weeks with sessions taking place 2.5 (1.1) times per week, and all interventions lasted less than 1 year. Conclusions and Relevance: In this study, short-term multidomain interventions (<1 year) were associated with improvements in global cognition, executive function, memory, and verbal fluency compared with single interventions in older adults with MCI.

Evaluation of Clinical Practice Guidelines on Fall Prevention and Management for Older Adults: A Systematic Review.

Importance: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. Objectives: To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. Evidence Review: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. Findings: Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. Conclusions and Relevance: This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.

New horizons in falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.

CCCDTD5 recommendations on early non cognitive markers of dementia: A Canadian consensus.

INTRODUCTION: Cognitive impairment is the hallmark of Alzheimer's disease (AD) and related dementias. However, motor decline has been recently described as a prodromal state that can help to detect at-risk individuals. Similarly, sensory changes, sleep and behavior disturbances, and frailty have been associated with higher risk of developing dementia. These clinical findings, together with the recognition that AD pathology precedes the diagnosis by many years, raises the possibility that non-cognitive changes may be early and non-invasive markers for AD or, even more provocatively, that treating non-cognitive aspects may help to prevent or treat AD and related dementias. METHODS: A subcommittee of the Canadian Consensus Conference on Diagnosis and Treatment of Dementia reviewed areas of emerging evidence for non-cognitive markers of dementia. We examined the literature for five non-cognitive domains associated with future dementia: motor, sensory (hearing, vision, olfaction), neuro-behavioral, frailty, and sleep. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assign the strength of the evidence and quality of the recommendations. We provide recommendations to primary care clinics and to specialized memory clinics, answering the following main questions: (1) What are the non-cognitive and functional changes associated with risk of developing dementia? and (2) What is the evidence that sensory, motor, behavioral, sleep, and frailty markers can serve as potential predictors of dementia? RESULTS: Evidence supported that gait speed, dual-task gait speed, grip strength, frailty, neuropsychiatric symptoms, sleep measures, and hearing loss are predictors of dementia. There was insufficient evidence for recommending assessing olfactory and vision impairments as a predictor of dementia. CONCLUSIONS: Non-cognitive markers can assist in identifying people at risk for cognitive decline or dementia. These non-cognitive markers may represent prodromal symptoms and several of them are potentially amenable to treatment that might delay the onset of cognitive decline.

Dual decline in gait speed and cognition is associated with future dementia: evidence for a phenotype.

BACKGROUND: concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of 'dual decliners', those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. METHODS: prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants' gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t-test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. RESULTS: among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23-7.93, P = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. CONCLUSION: older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition.

Mapping Associations Between Gait Decline and Fall Risk in Mild Cognitive Impairment.

OBJECTIVES: Compared to their cognitively healthy counterparts, older adults with mild cognitive impairment (MCI) exhibit higher risk of falls, specifically with injuries. We sought to determine whether fall risk in MCI is associated with decline in higher-level brain gait control. DESIGN: Longitudinal study. SETTING: Community-dwelling adults from the Gait and Brain Study Cohort. PARTICIPANTS: A total of 110 participants, aged 65 years or older, with MCI. MEASUREMENTS: Biannual assessments for medical characteristics, cognitive performance, fall incidence, and gait performance for up to 7 years. Seven spatiotemporal gait parameters, including variabilities, were recorded using a 6-meter electronic walkway. Principal components analysis was used to identify independent gait domains related to higher-level (pace and variability domains) and lower-level (rhythm domain) brain control. Associations between gait decline and incident falls were studied with Cox regression models adjusted for baseline covariates. RESULTS: Of participants enrolled, 40% experienced at least one fall (28% of them with injuries) over a mean follow-up of 31.6 ± 23.9 months. From the pace domain, slower gait speed (adjusted hazard ratio [aHR] per 10-cm/s decrease = 4.62; 95% confidence interval [CI] = 1.84-11.61; P = .001) was associated with severe injurious falls requiring emergency room (ER) visit; from the variability domain, stride time variability (aHR per 10% increase during follow-up = 2.17; 95% CI = 1.02-4.63; P = .04) was associated with higher risk of all injurious falls. Rhythm domain was not associated with fall risk. Decline in pace domain was significantly associated with falls with ER visit (aHR = 3.67; 95% CI = 1.46-9.19; P = .005). After adjustments for multiple comparisons, gait speed and pace domain remained significantly associated with falls with ER visits. No statistically significant associations were found between gait domains and overall falls (P ≥ .06). CONCLUSION: Higher risk of injurious falls in older adults with MCI is associated with decline in gait parameters related to higher-level brain control. J Am Geriatr Soc 68:576-584, 2020.

Are Cognitive Subtypes Associated with Dual-Task Gait Performance in a Clinical Setting?

BACKGROUND: Poor dual-task gait (walking while performing a cognitively demanding task) has been linked to progression to dementia in older adults with mild cognitive impairment (MCI). However, many of these findings come from research environments; gait performance across the cognitive spectrum has not previously been studied in a clinical setting. OBJECTIVE: To examine whether patients from a memory clinic show differences in usual and dual-task gait speed and dual-task cost (DTC) based on cognitive diagnosis. METHODS: Patients in the Aging Brain and Memory Clinic (London, ON) performed a usual gait walk and three dual-task gait walks: counting backwards by ones, naming animals, and counting backwards by seven (serial sevens) out loud. Patients were timed with a stopwatch over a six-meter path marked on the floor. One-way ANOVA was performed to evaluate associations between gait speed and DTC (%) across groups. RESULTS: One hundred ninety-four patients with subjective cognitive impairment (SCI; n = 46), MCI (n = 77), or dementia (n = 71) were assessed. Performance in usual (p < 0.001) and dual-task gait speed (counting gait p < 0.001; naming animals p < 0.001; serial sevens p = 0.004) decreased across the spectrum of cognitive impairment. Patients with dementia had significantly higher DTC in both counting gait (p = 0.02) and naming animals (p = 0.04) conditions compared with patients with SCI and MCI, who had statistically similar DTC in all conditions. CONCLUSION: Dual-task gait performance significantly declines across the cognitive spectrum in a clinical setting. Dual-task gait testing may be used in conjunction with traditional assessments for diagnosing cognitive impairments.

Polypharmacy, Gait Performance, and Falls in Community-Dwelling Older Adults. Results from the Gait and Brain Study.

BACKGROUND AND OBJECTIVES: Polypharmacy, defined as the use of five or more medications, has been repeatedly linked to fall incidence, and recently it was cross-sectionally associated with gait disturbances. Our objectives were to evaluate cross-sectional and longitudinal associations between polypharmacy and gait performance in a well-established clinic-based cohort study. We also assessed whether gait impairments could mediate associations between number of medications and fall incidence. DESIGN: Prospective cohort of community-dwelling older adults, with 5 years of follow-up. SETTING: Geriatric clinics in an academic hospital in London, ON, Canada. PARTICIPANTS: Community-dwelling older adults aged 65 and older (n = 249; 76.6 ± 8.6 y; 63% women). MEASUREMENTS: Number of medications, quantitative spatiotemporal gait parameters, and fall incidence during follow-up. RESULTS: The number of medications was cross-sectionally associated with poor gait performance (slow gait, speed p < .001; higher variability, p < .001; and higher stride, p < .001; step, p = .013, and double support times, p < .001). Prospectively, the number of medications was associated with overall gait decline (odds ratio = 1.23; 95% confidence interval [CI] = 1.13-1.33; p < .001), faster gait decline (hazard ratio = 4.62; 95%CI = 1.82-11.73; p < .001), and higher falls incidence (p = .006). These associations remained true after adjusting for age, sex, and accounting for "confounding by indication bias" by using a comorbidity propensity score adjustment. Each additional medication taken, significantly increased gait decline risk by 12% to 16% and fall incidence risk by 5% to 7%. Mediation analyses revealed that gait impairments in stride length, step length, and step width mediated the strength of the association between medications and fall incidence. CONCLUSION: Polypharmacy was cross-sectionally associated with poor gait performance and longitudinally associated with gait decline and fall incidence. Despite our use of propensity matching, confounding by indication could have influenced the results. Quantitative spatial gait parameters performance mediated the strength of the association between medications and falls, suggesting a role of gait disturbances in the medication-related falls pathway.

Mild Cognitive Impairment Affects Obstacle Negotiation in Older Adults: Results from "Gait and Brain Study".

BACKGROUND: Older adults with Mild Cognitive Impairment (MCI) are at higher risk of falls and injuries, but the underlying mechanism is poorly understood. Inappropriate anticipatory postural adjustments to overcome balance perturbations are affected by cognitive decline. However, it is unknown whether anticipatory gait control to avoid an obstacle is affected in MCI. OBJECTIVE: Using the dual-task paradigm, we aim to assess whether gait control is affected during obstacle negotiation challenges in older adults with MCI. METHODS: Seventy-nine participants (mean age = 72.0 ± 2.7 years; women = 30.3%) from the "Gait and Brain Study" were included in this study (controls = 27; MCI = 52). In order to assess the anticipatory control behaviour for obstacle negotiation, a 6-m electronic walkway embedded with sensors recorded foot prints to measure gait speed and step length variability, during early (3 steps before the late phase) and late (3 steps before the obstacle) pre-crossing phases of an ad hoc obstacle, set at 15% of participant's height. Participants walked under single- and dual-task gait (counting backwards by 1's from 100 while walking) conditions. Three-way mixed repeated-measures analysis of variance models examined differences in gait performance between groups when transitioning between pre-crossing phases towards an obstacle during single- and dual-task conditions. Analyses were adjusted for age, sex, years of education, lower limb function, fear of falling, medical status, depressive symptoms, baseline gait speed and executive function. RESULTS: A significant three-way interaction among groups, pre-crossing phases and task showed that participants with MCI attenuated the gait deceleration (p = 0.02) and performed fewer step length adjustments (p = 0.03) when approaching the obstacle compared with controls while dual-tasking. These interactions were attenuated when executive function performance was added as a covariate in the adjusted statistical model. CONCLUSION: Older adults with MCI attenuate the anticipatory gait adjustments needed to avoid an obstacle when dual-tasking. Deficits in higher-order cognitive processing may limit obstacle negotiation capabilities in MCI populations, being a potential falls risk factor.

Guidelines for Gait Assessments in the Canadian Consortium on Neurodegeneration in Aging (CCNA).

BACKGROUND: Motor and cognitive impairments are common among older adults and often co-exist, increasing their risk of dementia, falls, and fractures. Gait performance is an accepted indicator of global health and it has been proposed as a valid motor marker to detect older adults at risk of developing mobility and cognitive declines including future falls and incident dementia. Our goal was to provide a gait assessment protocol to be used for clinical and research purposes. METHODS: Based on a consensus that identified common evaluations to assess motor-cognitive interactions in community-dwelling older individuals, a protocol on how to evaluate gait in older adults for the Canadian Consortium on Neurodegeneration in Aging (CCNA) was developed. RESULTS: The CCNA gait assessment includes preferred and fast pace gait, and dual-task gait that comprises walking while performing three cognitively demanding tasks: counting backwards by ones, counting backwards by sevens, and naming animals. This gait protocol can be implemented using an electronic-walkway, as well as by using a regular stopwatch. The latter approach provides a simple manner to evaluate quantitative gait performance in clinics. CONCLUSIONS: Establishing a standardized gait assessment protocol will help to assess motor-cognitive interactions in aging and neurodegeneration, to compare results across studies, and to feasibly implement and translate gait testing in clinics for detecting impending cognitive and mobility decline.

Motor and Cognitive Trajectories Before Dementia: Results from Gait and Brain Study.

OBJECTIVES: To compare the trajectories of motor and cognitive decline in older adults who progress to dementia with the trajectories of those who do not. To evaluate the added value of measuring motor and cognitive decline longitudinally versus cross-sectionally for predicting dementia. DESIGN: Prospective cohort study with 5 years of follow-up. SETTING: Clinic based at a university hospital in London, Ontario, Canada. PARTICIPANTS: Community-dwelling participants aged 65 and older free of dementia at baseline (N=154). MEASUREMENTS: We evaluated trajectories in participants' motor performance using gait velocity and cognitive performance using the MoCA test twice a year for 5 years. We ascertained incident dementia risk using Cox regression models and attributable risk analyses. Analyses were adjusted using a time-dependent covariate. RESULTS: Overall, 14.3% progressed to dementia. The risk of dementia was almost 7 times as great for those whose gait velocity declined (hazard ratio (HR)=6.89, 95% confidence interval (CI)=2.18-21.75, p=.001), more than 3 times as great for those with cognitive decline (HR=3.61, 95% CI=1.28-10.13, p=.01), and almost 8 times as great in those with combined gait velocity and cognitive decline (HR=7.83, 95% CI=2.10-29.24, p=.002), with an attributable risk of 105 per 1,000 person years. Slow gait at baseline alone failed to predict dementia (HR=1.16, 95% CI=0.39-3.46, p=.79). CONCLUSION: Motor decline, assessed according to serial measures of gait velocity, had a higher attributable risk for incident dementia than did cognitive decline. A decline over time of both gait velocity and cognition had the highest attributable risk. A single time-point assessment was not sufficient to detect individuals at high risk of dementia.

Association of Dual-Task Gait With Incident Dementia in Mild Cognitive Impairment: Results From the Gait and Brain Study.

Importance: Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI. Objective: To determine whether a dual-task gait test is associated with incident dementia in MCI. Design, Setting, and Participants: The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016. Main Outcomes and Measures: Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity - dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition. Results: Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (<0.8 m/second) was not associated with progression to dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized. Conclusions and Relevance: Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI. Trial Registration: clinicaltrials.gov: NCT03020381.

Population Differences at MHC Do Not Explain Enhanced Resistance of Song Sparrows to Local Parasites.

Infectious disease represents an emerging threat to natural populations, particularly when hosts are more susceptible to novel parasites (allopatric) than to parasites from the local area (sympatric). This pattern could arise through evolutionary processes (host populations become adapted to their local parasites and genetically differentiated from other populations at immune-related loci) and/or through ecological interactions (host individuals develop resistance to local parasites through previous exposure). The relative importance of these candidate mechanisms remains unclear. In jawed vertebrates, genes of the major histocompatibility complex (MHC) play a fundamental role in immunity and are compelling candidates for spatially varying selection. We recently showed that song sparrows (Melospiza melodia) are more susceptible to allopatric than to sympatric strains of malaria (Plasmodium). In the current study, to determine whether population differences at MHC explain this pattern, we characterized the peptide-binding regions of MHC (classes I and II) of birds that did or did not become infected in the previous experiment. We recovered up to 4 alleles per individual at class I, implying at least 2 loci, and up to 26 alleles per individual at class II, implying at least 13 loci. Individuals with more class I alleles were less likely to become infected by Plasmodium, consistent with parasite-mediated balancing selection. However, we found no evidence for population genetic differentiation at either class of MHC, based on 36 individuals sequenced. Resistance to sympatric parasites previously described for this system likely stems from individuals' prior immune experience, not from population differentiation and locally protective alleles at MHC.

Song sparrows Melospiza melodia have a home-field advantage in defending against sympatric malarial parasites.

Hosts and parasites interact on both evolutionary and ecological timescales. The outcome of these interactions, specifically whether hosts are more resistant to their local parasites (sympatric) than to parasites from another location (allopatric), is likely to affect the spread of infectious disease and the fitness consequences of host dispersal. We conducted a cross-infection experiment to determine whether song sparrows (Melospiza melodia) have an advantage in dealing with sympatric parasites. We captured birds from two breeding sites 437 km apart, and inoculated them with avian malaria (Plasmodium spp.) cultured either from their capture site or from the other site. Infection risk was lower for birds exposed to sympatric than to allopatric Plasmodium lineages, suggesting that song sparrows may have a home-field advantage in defending against local parasite strains. This pattern was more pronounced at one capture site than at the other, consistent with mosaic models of host-parasite interactions. Home-field advantage may arise from evolutionary processes, whereby host populations become adapted to their local parasites, and/or from ecological interactions, whereby host individuals develop resistance to the local parasites through previous immune exposure. Our findings suggest that greater susceptibility to novel parasites may represent a fitness consequence of natal dispersal.

Effects of early-developmental stress on growth rates, body composition and developmental plasticity of the HPG-axis.

In altricial songbirds, food restriction in early development has adverse effects on various physiological systems. When conditions improve birds can accelerate growth, but this compensatory strategy is associated with long-term adverse consequences. One system affected by altered growth rates is the hypothalamic-pituitary-gonadal (HPG) axis. Here, we subjected European starlings, Sturnus vulgaris, to an unpredictable food manipulation from 35 to 115days of age. We assessed the effects of the treatment by measuring overall body mass and body composition during and following the treatment period (i.e., accelerated growth). In adulthood, we measured the long-term effects of the treatment on overall body mass, testis volume, and HPG axis function in both sexes by quantifying androgen levels before and after a gonadotropin-releasing hormone (GnRH) challenge. During the treatment period, treatment birds had less body fat than controls. Following the treatment period, treatment birds weighed more than controls, but these gains were attributed to changes in lean mass. In adulthood, treatment males had lower baseline androgen levels, but there was no difference in peak androgen levels compared to controls. Treatment females did not differ from controls on any of the androgen measures. However, females that accelerated growth faster following the termination of the treatment had lower integrated androgen levels. When faced with limited developmental resources, birds may alter the developmental trajectory of physiological systems as a compensatory strategy. Such a strategy may have long-term consequences on endocrine regulation that could affect courtship and reproductive behaviors.